This invention relates to a method of preparing an inhibitor of endothelial cell growth. The products of this method are useful in treating or preventing ocular neovascularization and reducing neovascularization in tumors.
Endothelial cells are a key component of blood vessels. Proliferation of vascular endothelial cells play an important role in many biological processes. These include wound healing, formation of inflammatory granulation tissue, the organization of thrombi, the healing of large vessel defects and the repopulation of endothelium in grafts. Normal adult vascular endothelium represents a slowly renewing population of cells. However several pathological situations result in abnormal endothelial cell proliferation with the formation of unwanted new blood vessels. This latter process is called "neovascularization".
Neovascularization of ocular tissues is one of the most important clinical problems in opthalmology. In many disease states the various mature vascular beds of the eye grow beyond their normal limits. Diabetes mellitus is responsible for loss of vision in 12% of the total United States blind population and for 20% of the cases of new blindness in adults between the ages of 45 and 74. Retinopathy, the major cause of blindness in diabetics is responsible in about 84% of blind diabetic patients. At some critical point capillary endothelium begins to proliferate. The new retinal vessels may penetrate the internal limiting membrane of the retina and enter the vitreous where devastating hemorrhages may occur, leading to blindness. During the active, proliferative phase of diabetic retinopathy, neovascularization is also accompanied by fibrous tissue formation, which, when connected between the retinal and vitreous surfaces, can produce tractional elevation and tearing of the retina with subsequent retinal detachment. In the case of diabetic retinopathy, hemorrhage into the vitreous caused by traction on the new blood vessels is treated by removal of the vitreous. Retinal detachment is also sometimes treated by surgery.
The growth of solid tumors has long been recognized to be dependent on the ability of the tumor to induce the formation of new blood vessels by their hosts. The host blood vessels vascularize the solid tumor and provide it with nutrients which allow continued tumor growth.
One object of this invention is to provide an inhibitor of endothelial cell growth.
Another object of this invention is to provide such an inhibitor which will prevent neovascularization in ocular tissue and solid tumors.
Still another object of this invention is to reduce the need for surgery in diabetic retinopathy.
Further objects and advantages of this invention will be apparent from the description and claims which follow.